Alexey M. Kopylov, Kopylov A., Zavyalova E., Turashev A., Golovin A. and Pavlova G.
Apto-Pharm Ltd, Chemistry Department Lomonosov Moscow State University, Russia
Drug targeting depends on ability to create molecule which could tightly and highly specifically interacts (recognize) with target, in other words - molecular recognition elements (MoRE). Balancing on bilateral paradigm of low molecular weight substances vs high molecular weight substances could favor intermediate type - oligomers, like peptides or oligonucleotides. One of example of therapeutic nucleic acids is aptamer - oligonucleotide which could recognize target due to specific 3D structure. Attractive academic potential of aptamers over antibodies has to be proved by extensive preclinical trials. We have explored pharmacological properties of original bipartite DNA aptamer to human thrombin, TROMBIVEB®, as well as comparing of TROMBIVEB® with other known thrombin DNA aptamers and commercial peptide inhibitor bivalirudin - anticoagulant on the market. Before discussing PD and PK it is critical mentioning production criteria for intravenous intervention. For pharmacodynamics, in addition to routine trials, original test has been developed, i.e. in vivo model for visualizing and measuring of thrombosis alive. Efficiency was tested in animals, especially in marmoset monkeys. We also run standard trials showing fast pharmacokinetics, low toxicity, low immunogenicity, good safety margins, allowing to plan GMP production for further trials.
Keywords: DNA aptamer, human thrombin, bivalirudin, anticoagulant, preclinical trials.